Wolman disease is a rare autosomal recessive disorder that results in the complete functional loss of the acid lipase enzyme. Hence, it is a part of lysosomal acid lipase deficiency (LAL-D). Infants with this disease typically present with a few key features: failure to thrive, vomiting, abdominal distension, steatorrhea, and hepatosplenomegaly. It is an exceedingly rare disease, occurring in only 1 of every 500,000 live births.
Among the first signs in children with Wolman disease are hepatosplenomegaly and enlarged lymph nodes, which are caused by the accumulation of lipids in these organs. This disease typically causes young patients to be unable to achieve normal age-adjusted height and weight percentiles. The toxic accumulation of lipids in the body can cause complications such as respiratory failure and hepatic cirrhosis. If left untreated, it almost always results in death within the first year of life, with the cause of death being malabsorption and diarrhea.
If a physician suspects Wolman disease in a child, a diagnosis can be made based on radiological findings and lab results. Shenoy et al stated, “Diagnosis of this condition is based on both laboratory parameters and its unique imaging features.” One of the most common radiological findings in Wolman disease is the calcification of enlarged adrenal glands, which is seen in about half of cases. This can be observed readily on abdominal X-ray or ultrasound, though computed tomography (CT) scans yield clearer results and can identify other LAL-D-related abnormalities. Blood tests should corroborate those findings, with elevated triglyceride and cholesterol levels. In addition, anemia, low platelets, and a deranged liver profile are also usually found.
Read more about LAL-D epidemiology
In elderly patients, LAL-D usually presents itself as cholesteryl ester storage disease. It differs from Wolman disease in that there is at least some acid lipase enzyme activity, about 1% to 12%, while in Wolman disease, it is less than 1%. The partial activity of acid lipase enzyme activity in cholesteryl ester storage disease means that affected patients can present very differently from each other.
There is currently no curative treatment for Wolman disease. Current treatment regimens are aimed at reducing complications while offering patients parenteral nutrition, dietary supplements, and steroids. The curative effects of bone marrow transplantations are currently inconclusive.
Needless to say, a more thorough understanding of this disease from a pathophysiology standpoint would increase our ability to create new therapies that are more targeted and effective. Two Afghan researchers presented the case of a young patient with Wolman disease and described some of the CT findings that they discovered in a case report published in Radiology Case Reports. We will take a closer look at the case study as presented and examine their investigative findings.
CT Findings in a 1-Year-Old
Researchers described a 1-year-old male child who presented with a history of malabsorption and abdominal distension. Physical examination revealed hepatosplenomegaly. There were no other aspects of the child’s history that suggested a genetic predisposition to a disease.
Due to the poor socioeconomic background of the patient’s family, the patient only underwent limited lab tests, which showed anemia (8 mg/dL) and leukopenia (4000/mm3). The platelet count was normal.
The young patient was brought to the radiology department for a CT scan. Below are the findings:
- Enlarged adrenal glands with stippled cortical calcifications
- Enlarged fatty liver
- Enlarged spleen
- Hyperenhancing thickened small bowel loops
- Perisplenic ascites
The CT findings of this patient are characteristic of Wolman disease. In Wolman disease, the adrenal glands can be observed to be calcified. Typically, calcification of the adrenal glands in other diseases causes them to either shrink or maintain their size; in Wolman disease, the adrenal glands are enlarged bilaterally. According to Dao et al, bilateral adrenal enlargement and calcification of the adrenal glands that are confined to the zona reticularis and inner fasciculata (sparing the zona glomerulosa, outer fasciculata, and medulla) are pathognomonic for Wolman disease.
Read more about LAL-D prognosis
The accumulation of lipids in the organs was likely the cause of the patient’s enlarged fatty liver and enlarged spleen. The thickened small bowel loops observed on the child’s CT scan were most likely caused by the infiltration of foamy histiocytes into the lamina propria of the gut.
Loss to Follow-Up and Its Implications
The most heartbreaking portion of the case study is this line: “The patient was lost to follow-up after imaging diagnosis.” Although unlikely to be the intention of the authors of the study, the lack of follow-up for a diagnosed case of Wolman disease opens up a discussion about existing global socioeconomic disparities that make it difficult for patients or their families to commit to a course of treatment that includes continuous medication, many follow-ups, and close monitoring. In countries where a diagnosis of Wolman disease might put a family in debt, patients and their families are indeed caught between a rock and a hard place. Even more devastating is that untreated Wolman disease likely results in death.
Although no curative treatment exists for Wolman disease, the ongoing research around this disease and LAL-D gives us hope that more targeted therapies will be developed in the near future.
Foladi N, Aien MT. CT features of Wolman disease (lysosomal acid lipase enzyme deficiency) – a case report. Radiol Case Rep. 2021;16(10):2857-2861. doi:10.1016/j.radcr.2021.06.084
Shenoy P, Karegowda L, Sripathi S, Mohammed N. Wolman disease in an infant. BMJ Case Rep. 2014;2014:bcr2014203656. doi:10.1136/bcr-2014-203656